Three-year median follow-up update of BGB-A317-2002-IIT: A phase 2 study of neoadjuvant tislelizumab plus gemcitabine and cisplatin in patients with cT2–T4aN0M0 muscle-invasive bladder cancer.

783 Background: A multicenter phase II trial evaluating neoadjuvant tislelizumab plus gemcitabine/cisplatin for patients with cT2–T4aN0M0 muscle-invasive bladder urothelial carcinoma (MIBC) demonstrated a favorable pathological response and safety. Here, we present the updated survival outcomes with a median follow-up of 3 years. Methods: Cisplatin-eligible patients with cT2–T4aN0M0 MIBC received tislelizumab 200 mg on day 1, cisplatin 70 mg/m 2 on day 2, and gemcitabine 1000 mg/m 2 on days 1 and 8 of a 21-day cycle for four cycles, followed by radical cystectomy (RC). Event-free survival (EFS) and overall survival (OS) were analyzed in the intention-to-treat (ITT) cohort, while recurrence-free survival (RFS) was analyzed among patients who underwent RC. Survival outcomes were estimated using Kaplan–Meier methods and stratified by pathological response (ypT0N0, ypTis/Ta/T1N0, and ≥ ypT2N0), PD-L1 expression, and tumor mutational burden (TMB). Results: From February 2021 to September 2022, 65 patients (12.3% female) were enrolled, and 57 underwent RC. The median follow-up was 42.2 months (IQR: 38.6–47.7). In the ITT population, the 3y-EFS was 73.4% (95% CI: 59.2–83.3%), and the 3y-OS was 82.5% (95% CI: 70.7–89.9%). Pathological response categories were significantly related to RFS (p < 0.0001): 3y-RFS for ypT0N0 responders was 86.9% (95% CI: 62.9–95.8%) vs 92.9% (95% CI: 59.1–99.0%) for ypTis/Ta/T1N0 vs 32.1% (95% CI: 9.5–57.9%) for ≥ ypT2N0. Eight patients who declined RC were alive at data cutoff, including 5 disease-free cases. Survival analysis stratified by TMB (cutoff at 14.8 mutations/Mb) showed significantly better EFS in the TMB-high group (N = 11) versus TMB-low (N = 35; log-rank test p = 0.031). Baseline PD-L1 expression was available for all ITT patients, and the EFS curves did not separate between PD-L1–high (N = 19) and PD-L1–low (N = 46) groups (log-rank test p = 0.599). Conclusions: Neoadjuvant tislelizumab plus gemcitabine/cisplatin demonstrated durable clinical benefit with sustained 3-year survival outcomes in patients with MIBC. Pathological response remained strongly associated with survival. High TMB, rather than PD-L1 expression, correlated with improved survival. Clinical trial information: ChiCTR2000037670.